The major area of study of this laboratory is the role of the epidermis as an immunological organ. We have found that epidermal Langerhans cells are derived from precursor cells in the bone marrow and play an essential role in many of the immunological reactions affecting the skin. When murine epidermal Langerhans cells are cultured for 2-3 days they become very potent antigen presenting cells for allogeneic and autologous T cells. We have therefore utilized cultured Langerhans cells for the generation of primary immune responses in resting unsensitized T cells. We have demonstrated that when cultured cells are modified with hapten, they can generate primary immune responses. The sensitized T cells thus generated respond preferentially to the same hapten in vitro. We have utilized phenotypic and functional assays to determine whether Langerhans cells from patients infected with HIV are altered. Studies to date indicate that Langerhans cells function at least as well as monocytes in presenting autologous, allogeneic and protein antigens to T cells from HIV-infected individuals. We have also been studying the early cell and molecular events which occur after hapten painting of skin of nonsensitized mice to identify potentially important Langerhans cell and keratinocyte alterations. In response to hapten painting, activated Langerhans cells appear in vivo and there is a differential upregulation of epidermally-derived cytokine mRNAs. We have found that Langerhans cell-derived IL-1~ is the earliest cytokine mRNA to be activated. Furthermore, we have identified that IP-10, MIP-2 and IL-10 are produced by keratinocytes. We have also demonstrated that IL-1~ plays a critical role in the "activation" of Langerhans cells. We are currently assessing cytokine mRNAs from human skin before and after in vivo or in vitro exposure to UV radiation. Studies to date indicate that IL-10 mRNAs can regularly be detected after UV radiation of human skin.